Moderna's BA.4/BA.5 Targeting Bivalent Booster, mRNA-1273.222, Meets Primary Endpoint of Superiority Against Omicron Variants Compared to Booster Dose of mRNA-1273 in Phase 2/3 Clinical Trial

In a Phase 2/3 trial in over 500 adults, mRNA-1273.222, induced significantly higher neutralizing antibody titers against BA.4/BA.5 compared to a booster dose of mRNA-1273

Results build upon data recently published in the New England Journal of Medicine that confirmed superiority of the Company's BA.1 bivalent vaccine, mRNA-1273.214, neutralizing titers against multiple Omicron variants compared to a booster dose of mRNA-1273

Both of the Company's updated bivalent boosters (mRNA-1273.214 and mRNA-1273.222) showed neutralizing titers against BQ.1.1, an emerging threat globally, in an exploratory analysis

Safety and tolerability of mRNA-1273.214 and mRNA-1273.222 were similar to a booster dose of
mRNA-1273 and adverse events were generally lower than the second dose of the primary series

CAMBRIDGE, MA / ACCESSWIRE / November 14, 2022 / Moderna, Inc., (NASDAQ:MRNA) a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that both of Moderna's bivalent Omicron-targeting booster candidates (mRNA-1273.214 and mRNA-1273.222) trigger a superior antibody response compared to a booster dose of mRNA-1273, the Company's prototype vaccine, against Omicron (BA.4/BA.5) in Phase 2/3 clinical trials. Both bivalent vaccines also met non-inferiority immunogenicity criteria to the original strain.

"We are pleased to see that both of our bivalent booster vaccine candidates offer superior protection against Omicron BA.4/BA.5 variants compared to our original booster, which is encouraging given COVID-19 remains a leading cause of hospitalization and death globally. In addition, the superior response against Omicron persisted for at least three months after the mRNA-1273.214 booster," said Stéphane Bancel, Moderna's Chief Executive Officer. "Our bivalent boosters also show, in research assays, neutralizing activity against BQ.1.1, an increasingly dominant emerging variant, confirming that updated vaccines have the potential to offer protection as the virus continues to evolve rapidly to escape our immunity."

In a Phase 2/3 study, a 50 µg booster dose of mRNA-1273.222 elicited a superior neutralizing antibody response against Omicron BA.4/BA.5 variants when compared to a 50 µg booster dose of mRNA-1273 in 511 previously vaccinated and boosted participants (ages 19-89 years). Participants received mRNA-1273.222 and mRNA-1273 approximately 9.5 months and 4.5 months after their prior vaccination, respectively. Pre-booster BA.4/BA.5 titers were similar between the mRNA-1273.222 and mRNA-1273 groups. The Omicron BA.4/BA.5 geometric mean titer (GMT) ratios of mRNA-1273.222 versus mRNA-1273 were 5.11 (95% CI: 4.10, 6.36) and 6.29 (95% CI: 5.27, 7.51) for participants with and without SARS-CoV-2 infection pre-booster, respectively. In all participants the GMT against Omicron BA.4/BA.5 was 4289 (95% CI: 3789.0, 4855.9) representing a 15.1-fold increase (95% CI: 13.3, 17.1) from pre-booster levels. For participants without prior infection, the GMT was 2325 (95% CI: 1321.2, 2812.7), representing a 26.4-fold increase (95% CI: 22.0, 31.9) and for those with prior infection, the GMT was 6965 (95% CI: 6043.7, 8025.4), representing a 9.8-fold (95% CI: 8.4, 11.4), increase from pre-booster levels. Importantly, results were consistent between participants aged 65 years and older and those aged 18 to 65.

In an exploratory analysis of approximately 40 participants using research assays, both bivalent vaccines demonstrated robust neutralizing activity against BQ.1.1, despite an approximately 5-fold drop in titers compared to BA.4/BA.5.

As published in the New England Journal of Medicine (NEJM), a 50 µg booster dose of mRNA-1273.214 elicited a superior neutralizing antibody response against Omicron BA.1 and Omicron BA.4/BA.5 compared to the booster dose of mRNA-1273, with superiority lasting through at least three months. In both groups, participants received the booster dose approximately 4.5 months after prior vaccination.

The frequency of adverse reactions with mRNA-1273.222 and mRNA-1273.214 were similar or lower than that of either a second or third dose of the original vaccine. Additionally, no new safety concerns were identified after approximately one month and three months of follow-up, respectively. These safety and immunogenicity data will be submitted for peer-reviewed publication and shared with regulators globally. These safety data are consistent with those recently published by the U.S. CDC and FDA in an analysis of over 211,000 individuals in the v-safe database¹.

About Moderna

In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna's capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID pandemic.

Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past eight years. To learn more, visit www.modernatx.com.

AUTHORIZED USE IN THE U.S.

Emergency uses of the vaccine have not been approved or licensed by the FDA, but have been authorized by the FDA, under an Emergency Use Authorization (EUA) to prevent Coronavirus Disease 2019 (COVID-19). The Moderna COVID-19 Vaccine is authorized in individuals 6 months of age and older as a primary series. The Moderna COVID-19 Vaccine, Bivalent is authorized as a booster dose in individuals 6 years of age and older.

IMPORTANT SAFETY INFORMATION

• Do not administer the vaccines to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the Moderna COVID-19 Vaccine.
• Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the Moderna COVID-19 Vaccine.
• Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second primary series dose or first booster dose.
• Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
• Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to the vaccines.
• The vaccines may not protect all vaccine recipients.
• Adverse reactions reported in clinical trials for children 6 years of age and older following administration of the Moderna COVID-19 Vaccine include pain at the injection site, fatigue, headache, myalgia, chills, nausea/vomiting, axillary swelling/tenderness, fever, erythema at the injection site, swelling at the injection site, and arthralgia.
• Adverse reactions in children 6 months through 5 years of age following administration of Moderna COVID-19 Vaccine include pain at the injection site, irritability/crying, fatigue, sleepiness, loss of appetite, headache, fever, myalgia, chills, nausea/vomiting, axillary (or groin) swelling/tenderness, arthralgia, erythema at the injection site, and swelling at the injection site.
• Anaphylaxis and other severe allergic reactions, myocarditis, pericarditis, and syncope have been reported following administration of the Moderna COVID-19 Vaccine during mass vaccination outside of clinical trials.
• The vaccination provider is responsible for mandatory reporting of certain adverse events to the Vaccine Adverse Event Reporting System (VAERS) online at https://vaers.hhs.gov/reportevent.html or by calling 1-800-822-7967.

Please see the Moderna COVID-19 Vaccine Fact Sheets for Healthcare Providers Administering Vaccine (Vaccine Providers) and Full Prescribing Information for:

• Booster dose for 6+ years
• Primary series for 12+ and Booster dose 18+ years
• Primary series for 6 - 11 years
• Primary series for 6 months - 5 years

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding: the Company's development of bivalent vaccine candidates against COVID-19 (mRNA-1273.214 and mRNA-1273.222); the ability of mRNA-1273.214 and mRNA-1273.222 to induce higher neutralizing antibody titers against Omicron variants than the Company's vaccine candidate against the ancestral strain of SARS-CoV-2 (mRNA-1273) over time and to trigger a strong immune response, regardless of prior infection and across age groups; the tolerability and safety profile for mRNA-1273.214 and mRNA-1273.222; the Company's bivalent booster strategy and its ability to offer strong protection against evolving variants of concern. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include those other risks and uncertainties described under the heading "Risk Factors" in Moderna's most recent Annual Report on Form 10-K and the Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, each filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release.

Moderna Contacts

Media:
Chris Ridley
Vice President, Corporate Communications & Media
617-800-3651
Chris.Ridley@modernatx.com

Investors:
Lavina Talukdar
Senior Vice President & Head of Investor Relations
617-209-5834
Lavina.Talukdar@modernatx.com

SOURCE: Moderna, Inc.